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PubMed2002

Stimulated biosynthesis of flavins in Photobacterium phosphoreum IFO 13896 and the presence of complete rib operons in two species of luminous bacteria.

Photobacterium phosphoreum IFO 13896 emits light strongly when cultured in medium containing 3% NaCl, but only weakly in medium containing 1% NaCl. It is known that dim or dark mutants appear frequently and spontaneously from this parent strain. To confirm that riboflavin biosynthesis is stimulated when the lux operon is active, the amount of light emitted and flavins synthesized under strongly or weakly light emitting conditions was determined. In comparison with the parent strain cultured in 3% NaCl, the same strain cultured in 1% NaCl emitted 1/36 the light and produced 1/4 the flavins, while three dim or dark mutants, M1, M2 and M3 cultured in 3% NaCl, emitted almost no light, 1/58 the light and 1/10 the light and produced 1/8, 1/5 and 1/3 the amount of flavins, respectively. From these results, we deduced that the genes for riboflavin synthesis, rib genes, are organized in an operon in this strain. In P. phosphoreum NCMB 844, it has been reported that a rib gene cluster is present just downstream of the lux operon. However, among rib genes, the gene for pyrimidine deaminase/pyrimidine reductase, ribD, was not found in this cluster. Because a complete rib operon seems to be necessary for efficient regulation at the transcriptional level, we expected ribD to be present downstream of this cluster and sequenced this region, using SUGDAT, Sequencing Using Genomic DNA As a Template. We could not find this gene but found a gene for hybrid-cluster protein (prismane protein). To find ribD in a different region, a partial ribD sequence was amplified and sequenced using a PCR-based method, and subsequently the genomic DNA was sequenced in both directions from this partial sequence using SUGDAT. Because ribC was found just downstream of ribD, we sequenced further downstream of ribC and confirmed that another complete set of rib genes, ribD, ribC, ribBA, and ribE, is present in P. phosphoreum. The presence of a complete rib operon in P. phosphoreum explains why this species can synthesize flavins at enhanced levels to sustain a strong light emission. Furthermore, we sequenced the rib operon in Vibrio fischeri, another representative luminous bacterium, in a manner similar to that described above, and confirmed that a complete operon is present also in this species. The organization of rib genes in an operon in the Proteobacteria gamma-subdivision is discussed.

Amino Acid Sequence↗
PubMed1981

Laser flash photolysis studies of electron transfer between semiquinone and fully reduced free flavins and horse heart cytochrome c.

Laser flash photolysis has been used to determine the second-order rate constants for the reduction of horse heart cytochrome c by the semiquinone and fully reduced forms of various flavin analogs. We find that substitution in the dimethylbenzene ring of the flavin causes appreciable changes in the rate constants, whereas substitutions at the N-10 position do not. Placing a charged phosphate group in the N-10 ribityl side chain leads to only small ionic strength effects on the rate constants, whereas a charged group attached to the dimethylbenzene ring produces a large ionic strength effect. These results can be accounted for by assuming that a productive collision between flavin and cytochrome involves an orientation that positions the aromatic ring--N-5 region of the flavin toward the heme crevice and the N-10--pyrimidine ring region away from it. Our observations have implications for mechanistic understanding of biological electron transfer reactions and are discussed in this context.

Animals↗
PubMed1984

Use of riboflavin-binding protein to investigate steric and electronic relationships in flavin analogs and models.

We have examined the affinity of two recently synthesized flavin analogs for the isoalloxazine binding site of riboflavin-binding protein (RBP). The results showed that pyrimidopteridines could bind to RBP (Kd 160-250 microM). This suggested that, at the FMN or FAD level, these analogs might also bind to other apoflavoproteins, thereby providing a high potential probe for flavin enzymology. In contrast, 4a,5-ring-opened isoalloxazines did not bind to RBP. However, 1,10a-ring-opened flavins bind with considerable avidity (Kd about 40 nM). Evidence is presented which indicates that the 4a,5-ring-opened species adopted a nonplanar configuration which, in turn, was responsible for the lack of affinity to RBP. Steric and electronic consequences of a 4a,5 ring opening are discussed in relation to flavin-dependent phenolic hydroxylases.

Binding Sites↗
PubMed1995

Chemical modification of the N-10 ribityl side chain of flavins. Effects on properties of flavoprotein disulfide oxidoreductases.

Three flavin derivatives modified at the 2'-position of the flavin N-10 ribityl side chain were synthesized: arabinoflavin, 2'-F-2'-deoxyarabinoflavin, and 2'-deoxyriboflavin. These were converted to the FAD level with FAD synthetase. Apoproteins of lipoamide dehydrogenase, glutathione reductase, and mercuric reductase, a family of flavoprotein oxidoreductases, were reconstituted with these flavins. Significant reduction of the catalytic activities was observed with the modified enzymes. During anaerobic reduction of the modified enzymes with substrate or dithiothreitol, decreased thermodynamic stability of the two-electron reduced enzyme forms (EH2) and the accumulation of the four-electron reduced forms (EH4) noted. This effect was more pronounced in case of arabino-FAD-reconstituted enzymes than with the other two. It was found that NAD+ binding influences the interaction between the flavin and the reduced disulfide in the 2'-F-arabino-FAD-lipoamide dehydrogenase, presumably by altering the relative oxidation-reduction potentials. 19F NMR data were obtained for different forms of the 2'-F-arabino-FAD-lipoamide dehydrogenase, which suggest marked conformational changes from one form to the other. The 19F NMR data for the oxidized forms of all three 2'-F-arabino-FAD proteins suggest that the fluorine experiences very similar chemical environments at the active sites.

Animals↗
PubMed2001

The photocycle of a flavin-binding domain of the blue light photoreceptor phototropin.

The plant blue light receptor, phot1, a member of the phototropin family, is a plasma membrane-associated flavoprotein that contains two ( approximately 110 amino acids) flavin-binding domains, LOV1 and LOV2, within its N terminus and a typical serine-threonine protein kinase domain at its C terminus. The LOV (light, oxygen, and voltage) domains belong to the PAS domain superfamily of sensor proteins. In response to blue light, phototropins undergo autophosphorylation. E. coli-expressed LOV domains bind riboflavin-5'-monophosphate, are photochemically active, and have major absorption peaks at 360 and 450 nm, with the 450 nm peak having vibronic structure at 425 and 475 nm. These spectral features correspond to the action spectrum for phototropism in higher plants. Blue light excitation of the LOV2 domain generates, in less than 30 ns, a transient approximately 660 nm-absorbing species that spectroscopically resembles a flavin triplet state. This putative triplet state subsequently decays with a 4-micros time constant into a 390 nm-absorbing metastable form. The LOV2 domain (450 nm) recovers spontaneously with half-times of approximately 50 s. It has been shown that the metastable species is likely a flavin-cysteine (Cys(39) thiol) adduct at the flavin C(4a) position. A LOV2C39A mutant generates the early photoproduct but not the adduct. Titrations of LOV2 using chromophore fluorescence as an indicator suggest that Cys(39) exists as a thiolate.

Cell Membrane↗
PubMed2002

FAD is a preferred substrate and an inhibitor of Escherichia coli general NAD(P)H:flavin oxidoreductase.

Escherichia coli general NAD(P)H:flavin oxidoreductase (Fre) does not have a bound flavin cofactor; its flavin substrates (riboflavin, FMN, and FAD) are believed to bind to it mainly through the isoalloxazine ring. This interaction was real for riboflavin and FMN, but not for FAD, which bound to Fre much tighter than FMN or riboflavin. Computer simulations of Fre.FAD and Fre.FMN complexes showed that FAD adopted an unusual bent conformation, allowing its ribityl side chain and ADP moiety to form an additional 3.28 H-bonds on average with amino acid residues located in the loop connecting Fbeta5 and Falpha1 of the flavin-binding domain and at the proposed NAD(P)H-binding site. Experimental data supported the overlapping binding sites of FAD and NAD(P)H. AMP, a known competitive inhibitor with respect to NAD(P)H, decreased the affinity of Fre for FAD. FAD behaved as a mixed-type inhibitor with respect to NADPH. The overlapped binding offers a plausible explanation for the large K(m) values of Fre for NADH and NADPH when FAD is the electron acceptor. Although Fre reduces FMN faster than it reduces FAD, it preferentially reduces FAD when both FMN and FAD are present. Our data suggest that FAD is a preferred substrate and an inhibitor, suppressing the activities of Fre at low NADH concentrations.

Binding Sites↗
PubMed2005

Dissecting the structural determinants of the stability of cholesterol oxidase containing covalently bound flavin.

Cholesterol oxidase from Brevibacterium sterolicum is a monomeric flavoenzyme catalyzing the oxidation and isomerization of cholesterol to cholest-4-en-3-one. This protein is a class II cholesterol oxidases, with the FAD cofactor covalently linked to the enzyme through the His(69) residue. In this work, unfolding of wild-type cholesterol oxidase was compared with that of a H69A mutant, which does not covalently bind the flavin cofactor. The two protein forms do not show significant differences in their overall topology, but the urea-induced unfolding of the H69A mutant occurred at significant lower urea concentrations than wild-type (approximately 3 versus approximately 5 M, respectively), and the mutant protein had a melting temperature approximately 10-15 degrees C lower than wild-type in thermal denaturation experiments. The different sensitivity of the various spectroscopic features used to monitor protein unfolding indicated that in both proteins a two-step (three-state) process occurs. The presence of an intermediate was more evident for the H69A mutant at 2 m urea, where catalytic activity and tertiary structure were lost, and new hydrophobic patches were exposed on the protein surface, resulting in protein aggregation. Comparative analysis of the changes occurring upon urea and thermal treatment of the wild-type and H69A protein showed a good correlation between protein instability and the elimination of the covalent link between the flavin and the protein. This covalent bond represents a structural device to modify the flavin redox potentials and stabilize the tertiary structure of cholesterol oxidase, thus pointing to a specific meaning of the flavin binding mode in enzymes that carry out the same reaction in pathogenic versus non-pathogenic bacteria.

Anilino Naphthalenesulfonates↗
PubMed1987

Flavin catabolites: identification and quantitation in human urine.

Riboflavin is the primary flavin excreted in human urine but significant amounts of 7 alpha-hydroxyriboflavin and lesser amounts of 8 alpha-hydroxyriboflavin are present and reflect tissue microsomal oxidations. A newly found flavin catabolite of an 8 alpha-sulfonyl type may reflect intake and/or turnover of such thioether-linked flavin as occurs in monoamine oxidase. Additionally, lesser amounts of 10-hydroxyethylflavin (indicative of intestinal microbial action on the vitamin) and traces of lumiflavin (arising from photodecomposition) constitute part of the remaining flavin, which acutely reflects level of intake.

Adult↗
PubMed1985

Riboflavin requirement for growth, tissue saturation and maximal flavin-dependent enzyme activity in young rainbow trout (Salmo gairdneri) at two temperatures.

Two temperatures (10 degrees and 15 degrees C) and two fish stocks differing in growth potential were used to determine the dietary riboflavin requirement of young rainbow trout (Salmo gairdneri) on the basis of growth parameters, tissue saturation and a flavin-dependent biochemical function. Two experiments were conducted with purified diets based on vitamin-free casein. In experiment 1, fry (initially 2.0 g/fish) were fed, for 16 wk at 15 degrees C, diets containing 0.6, 2.6, 3.6, 4.6, 5.6 or 6.6 mg riboflavin per kilogram diet. In experiment 2, fry (initially 1.7-1.8 g/fish) were held at either 10 degrees or 15 degrees C and fed, for 10 wk, diets containing 0.7, 2.7, 3.7, 4.7, 6.7 or 8.7 mg riboflavin per kilogram. The riboflavin requirements for maximal growth rate, liver flavin saturation, spleen and head kidney flavin saturation and maximal hepatic D-amino-acid oxidase activity were 3.6, 4.6, 6.6 and 5.6 mg/kg diet, respectively, in a diet containing 40% crude protein and 15% ether extract. The requirements were not affected by temperature or by genetically determined differences in maximal growth rate. When expressed on a dietary energy basis, the riboflavin requirements of the trout for maximal growth rate and liver flavin saturation appear similar to those of several homeothermic species.

Animal Nutritional Physiological Phenomena↗
PubMed1979

A study of flavin-protein and flavoprotein-ligand interactions. Binding aspects and spectral properties of D-amino acid oxidase and riboflavin binding protein.

To study flavin-protein and flavoprotein-ligand interaction, the absorption, CD and MCD spectra of riboflavin, FAD, roseoflavin, the complexes of riboflavin and roseoflavin with riboflavin binding protein(RBP),D-amino acid oxidase(D-AO) and its complexes with ligands were observed in the spectral region of 310-600 nm and the binding properties of D-AO with di-substituted benzoate derivatives and of RBP with roseoflavin were also measured. The dimer of D-amino acid oxidase has a higher affinity for di-substituted benzoate derivatives than the monomer. The change in the absorption of FAD in D-AO caused by the binding of the first ligand to the dimer, which can bind two ligands, was similar to that caused by the binding of the second ligand. Roseoflavin could bind to RBP in a 1 : 1 ratio and the dissociation constant was 3.8 x 10(-8)M. The protein fluorescence of RBP was quenched by about 86% due to complex formation with roseoflavin. The MCD spectra showed similar patterns for all molecular complexes of riboflavin and FAD, with two negative extrema of ellipticity which probably correspond to the Faraday B-term, but the Faraday A-term could not be observed, suggesting that there was no degeneracy in the excited state of flavins. It is also suggested, based on a comparison of the absorption, CD and MCD spectra, that the vibronic structure of flavin was modified differently by each flavin-protein or flavoprotein-ligand interaction. Comparison of the absorption, CD and MCD spectra(310-600 nm) for roseoflavin and the roseoflavin-RBP complex revealed that there were five spectral components around 320, 340, 400, 500, and 550 nm in roseoflavin.

Carrier Proteins↗
PubMed2006

Crystal structure of human D-amino acid oxidase: context-dependent variability of the backbone conformation of the VAAGL hydrophobic stretch located at the si-face of the flavin ring.

In the brain, the extensively studied FAD-dependent enzyme D-amino acid oxidase (DAO) degrades the gliotransmitter D-serine, a potent activator of N-methyl-D-aspartate type glutamate receptors, and evidence suggests that DAO, together with its activator G72 protein, may play a key role in the pathophysiology of schizophrenia. Indeed, its potential clinical importance highlights the need for structural and functional analyses of human DAO. We recently succeeded in purifying human DAO, and found that it weakly binds FAD and shows a significant slower rate of flavin reduction compared with porcine DAO. However, the molecular basis for the different kinetic features remains unclear because the active site of human DAO was considered to be virtually identical to that of porcine DAO, as would be expected from the 85% sequence identity. To address this issue, we determined the crystal structure of human DAO in complex with a competitive inhibitor benzoate, at a resolution of 2.5 Angstrom. The overall dimeric structure of human DAO is similar to porcine DAO, and the catalytic residues are fully conserved at the re-face of the flavin ring. However, at the si-face of the flavin ring, despite the strict sequence identity, a hydrophobic stretch (residues 47-51, VAAGL) exists in a significantly different conformation compared with both of the independently determined porcine DAO-benzoate structures. This suggests that a context-dependent conformational variability of the hydrophobic stretch accounts for the low affinity for FAD as well as the slower rate of flavin reduction, thus highlighting the unique features of the human enzyme.

Amino Acid Motifs↗
PubMed1977

On the structure of flavin-oxygen intermediates involved in enzymatic reactions.

During the catalytic reactions of flavoprotein hydroxylases and bacterial luciferase, flavin peroxides are formed as intermediates [see Massey, V. and Hemmerich, P. (1976) in The Enzymes, 3rd edn (P. Boyer, ed.) pp. 421--505, Academic Press, New York]. These intermediates have been postulated to be C(4a) derivatives of the flavin coenzyme. To test this hypothesis, modified flavin coenzymes carrying an oxygen substituent at position C(4a) of the isoalloxazine ring were synthesized. They are tightly bound by the apoenzymes of D-amino acid oxidase, p-hydroxybenzoate hydroxylase and lactate oxidase; the resulting complexes show spectral properties closely similar to those of the transient oxygen adducts of the hydroxylases. The optical spectra of the lumiflavin model compounds were found to be highly dependent on the solvent environment and nature of the subsituents. Under appropriate conditions they simulate satisfactorily the spectra of the transient enzymatic oxygen adducts. The results support the proposal that the primary oxygen adducts formed with these flavoproteins on reaction of the reduced enzymes with oxygen are flavin C(4a) peroxides.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1983

Succinate dehydrogenase mutants of Bacillus subtilis lacking covalently bound flavin in the flavoprotein subunit.

Succinate dehydrogenase consists of two unequal subunits; Fp and Ip. An FAD group is covalently linked to a histidyl residue in the Fp subunit. The mechanism by which flavin is attached to protein is not known. Covalently bound flavin was studied in wild-type and succinate-dehydrogenase-negative Bacillus subtilis. The Fp subunit of succinate dehydrogenase was found to be the only (major) flavinylated protein in the cell. Mutants lacking covalently bound flavin and still containing the Fp polypeptide are described. It is shown that the flavin is not essential for assembly and membrane binding of succinate dehydrogenase in B. subtilis.

Bacillus subtilis↗
PubMed1993

Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the presence of magnesium perchlorate.

We have investigated the photosensitized monomerization of the cis,syn-cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5-deazaflavin derivative as photosensitizer. Although little monomerization of the dimer is induced by photoexcitation of the flavins in the absence of any additives, the flavins can function as an efficient photosensitizer in the presence of magnesium perchlorate. Mechanistic studies involving spectroscopic, quantum-yield and flash-photolysis measurements demonstrated that the photosensitized monomerization exclusively proceeds through electron transfer from the dimer to the triplet flavins complexed with Mg2+. The effects of magnesium perchlorate are compared with those on the chloranil-photosensitized monomerization and also with the effects of HClO4 on the flavin-photosensitized reaction.

Flavins↗
PubMed1996

Biochemical characterization of NfsA, the Escherichia coli major nitroreductase exhibiting a high amino acid sequence homology to Frp, a Vibrio harveyi flavin oxidoreductase.

We identified the nfsA gene, encoding the major oxygen-insensitive nitroreductase in Escherichia coli, and determined its position on the E. coli map to be 19 min. We also purified its gene product, NfsA, to homogeneity. It was suggested that NfsA is a nonglobular protein with a molecular weight of 26,799 and is associated tightly with a flavin mononucleotide. Its amino acid sequence is highly similar to that of Frp, a flavin oxidoreductase from Vibrio harveyi (B. Lei, M. Liu, S. Huang, and S.-C. Tu, J. Bacteriol. 176:3552-3558, 1994), an observation supporting the notion that E. coli nitroreductase and luminescent-bacterium flavin reductase families are intimately related in evolution. Although no appreciable sequence similarity was detected between two E. coli nitroreductases, NfsA and NfsB, NfsA exhibited a low level of the flavin reductase activity and a broad electron acceptor specificity similar to those of NfsB. NfsA reduced nitrofurazone by a ping-pong Bi-Bi mechanism possibly to generate a two-electron transfer product.

Amino Acid Sequence↗
PubMed1997

Electron-nuclear double resonance spectroscopy investigation of 4-hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum: comparison with other flavin radical enzymes.

A FAD and [4Fe-4S]cluster-containing enzyme from Clostridium aminobutyricum catalyses the reversible dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA which involves the cleavage of an unactivated C-H bond at the beta-carbon. Transient oxidation of the substrate to an enoxy radical by FAD might facilitate the removal of this beta-proton, whereas no function could be attributed to the [4Fe-4S]cluster. In this paper the organic radical, which is formed by partial reduction of the enzyme with dithionite, was characterised as the neutral flavin semiquinone by EPR spectroscopy in H2O and D2O. The rapid electron-spin relaxation of the flavin semiquinone suggested a magnetic interaction with the [4Fe-4S]cluster. In order to obtain highly resolved information about nuclear spins in the vicinity of this paramagnetic centre, ENDOR spectroscopy was applied. The spectra were compared with those of the neutral semiquinone radicals of ferredoxin-NADP reductase and flavodoxin as well as with that of the anionic semiquinone radical of cholesterol oxidase. All ENDOR spectra showed strong couplings to the 8-methyl protons and to H-6 of the flavin. On addition of the substrates to the corresponding enzymes, the electron density changed significantly only at the 8-position. It decreased in the case of cholesterol oxidase and ferredoxin-NADP reductase, whereas an increase was observed with 4-hydroxybutyryl-CoA dehydratase. The results indicate an interaction of 4-hydroxybutyryl-CoA with the flavin as required by the proposed mechanism. Furthermore, the shift of electron density towards the benzoid ring of FAD in the dehydratase might be due to the location of the [4Fe-4S]cluster next to the 8-position as known from structurally characterised iron-sulfur flavoproteins.

Clostridium↗
PubMed1988

S-oxygenation of 7 alpha-thiomethylspironolactone by the flavin-containing monooxygenase.

Liver microsomes and highly purified flavin-containing monooxygenase from uninduced hogs catalyze the NADPH and oxygen-dependent S-oxygenation of 7 alpha-thiomethylspironolactone (7 alpha-TMSL), the major urinary metabolite of spironolactone, an effective antimineralocorticoid in humans. Studies on the biochemical mechanism of S-oxygenation of 7 alpha-TMSL suggests that this reaction is catalyzed exclusively by the flavin-containing monooxygenase and not by cytochrome P-450. This conclusion is based on the effects of selective cytochrome P-450 inhibitors as well as positive effectors and alternate substrates for the flavin-containing monooxygenase. The modest degree of stereoselective S-oxygenation of 7 alpha-TMSL may suggest steric inhibition of oxidation by the flavin-containing monooxygenase.

Animals↗
PubMedDate not supplied

The role of cytochromes P-450 and flavin-containing monooxygenase in the metabolism of (S)-nicotine by rabbit lung.

Rabbit lung microsomes metabolize (S)-nicotine primarily to (S)-nicotine delta 1',5'-iminium ion, which is the precursor of (S)-cotinine, the major urinary metabolite of (S)-nicotine in mammals. (S)-Nicotine-N'-oxide and normicotine are also produced as minor metabolites. alpha-Methylbenzylaminobenzotriazole, a mechanism-based suicide inhibitor of rabbit lung cytochromes P-450 2 and 6, inhibited (S)-nicotine oxidation in parallel with inhibition of benzphetamine N-demethylation and ethoxyresorufin O-deethylation. Pretreatment of rabbits with TCDD or Aroclor 1260 had no effect and markedly inhibited (S)-nicotine oxidation, respectively, strongly suggesting that alpha-methylbenzylaminobenzotriazole inhibition was due to inactivation of rabbit lung P-450 2. Reconstitution with cytochromes P-450 2 and 5 demonstrated that only P-450 2 was active toward (S)-nicotine, yielding predominantly the iminium ion, with smaller amounts of nornicotine, (S)-nicotine N'-oxide, and an unknown metabolite also detected. The purified rabbit lung P-450 2-catalyzed oxidation of (S)-nicotine to (S)-nicotine delta 1',5'-iminium ion exhibited a Km of 70 microM and a Vmax of 1.5 min. Covalent binding of (S)-5-3H-nicotine to rabbit lung macromolecules was dependent upon rabbit lung P-450 2-catalyzed formation of the iminium ion. Antibodies raised against P-450 2 inhibited the rabbit lung microsomal metabolism of (S)-nicotine to (S)-nicotine delta 1',5'-iminium ion by almost 95%. Titration of reconstituted P-450 2 with cytochrome b5 produced a concentration-dependent inhibition of nicotine oxidase activity. Increasing the ratio of NADH to NADPH in incubations containing lung microsomes and (S)-nicotine decreased the yield of the iminium ion, confirming the inhibitory effect of cytochrome b5 on the P-450 2-catalyzed alpha-carbon oxidation reaction. NADH alone did not support the lung microsomal metabolism of (S)-nicotine. N'-oxidation of (S]-nicotine is catalyzed by purified pig liver flavin-containing monooxygenase. A number of experiments involving the use of P-450 inhibitors, titration with NADPH-cytochrome P-450 reductase antibodies, and determination of the pH-enzyme activity profile suggested that rabbit lung flavin-containing monooxygenase contributes to a small amount of the N'-oxide produced by rabbit lung microsomes. Further examination with purified flavin-containing monooxygenase isolated from rabbit lung microsomes demonstrated that (S)-nicotine is a poor substrate for this enzyme. The low yield of N'-oxide, relative to other metabolites, in rabbit lung is uncharacteristic for most mammalian tissues and presumably reflects the unusual substrate specificity of rabbit lung flavin-containing monooxygenase.

Animals↗